The β-hemoglobinopathies are the most common monogenic disorders in humans, with symptoms arising after birth when the fetal γ-globin genes are silenced and the adult β-globin gene is activated. There is a growing appreciation that genome organization and the folding of chromosomes are key determinants of gene transcription. Underlying this function is the activity of transcriptional enhancers that increase the transcription of target genes over long linear distances. To accomplish this, enhancers engage in close physical contact with target promoters through chromosome folding or looping that is orchestrated by protein complexes that bind to both sites and stabilize their interaction. We find that enhancer activity can be redirected with concomitant changes in gene transcription. Both targeting the β-globin locus control region (LCR) to the γ-globin gene in adult erythroid cells by tethering and epigenetic unmasking of a silenced γ-globin gene lead to increased frequency of LCR/γ-globin contacts and reduced LCR/β-globin contacts. The outcome of these manipulations is robust, pancellular γ-globin transcription activation with a concomitant reduction in β-globin transcription. These examples show that chromosome looping may be considered a therapeutic target for gene activation in β-thalassemia and sickle cell disease.
Making genome edits in mammalian cellsChris Thorne
Looking at the kind of modifications that can be made in mammalian cells, and how at Horizon moving to a haploid model system has significantly improved efficiency of both editing and validation
Cancer Research: Effects of Insulin-like Factor -2 (IGF-2), Collagen, and Fib...Raul Soto
Cancer Research: Effects of Insulin-like Factor -2 (IGF-2), Collagen, and Fibronectin on the Proliferation and α5-Integrins Expression of the Rhabdomyosarcoma-derived (RD) Cell Line
Targeted T-cell receptor beta immune repertoire sequencing in several FFPE ti...Thermo Fisher Scientific
T-cell receptor beta (TCRβ) immune repertoire analysis by next-generation sequencing is a valuable tool for studies of the tumor microenvironment and potential immune responses to cancer immunotherapy. Here we describe a TCRβ sequencing assay that leverages the low sample input requirements of AmpliSeq library preparation technology to extend the capability of targeted immune repertoire sequencing to include FFPE samples which can often be degraded and in short supply
ABSTRACT- Coronary artery disease (CAD) is suspected as a leading cause of mortality in developed countries. Due
to cholesterol and fat deposit plaque is forming into the inner walls of the arteries of the heart, which leads to narrowing
of blood vessels of heart and reduce the blood flow rate into heart. Proprotein convertase subtilisin-like kexin type 9
(PCSK9) is one of the candidate gene that regulate lipoprotein retention pathway of CAD development. It is a newly
discovered serine protease that plays a key role in LDL-C homeostasis by mediating LDL receptor (LDLR). The LDL
receptor is breakdown through a post transcriptional mechanism and induces the production of very low-density
lipoprotein in the fasting state. The aim of this study was to investigate the frequency of single nucleotide
polymorphism (SNP) of PCSK9 gene of 155 CAD patients and 102 ages matched healthy controls. Serum lipids
including total cholesterol (TC), triglycerides (TG), HDL, LDL, and VLDL were analyzed. PCR-RFLP analysis was
carried out to genotype regions carrying Eam 1104I restriction site in the PCSK9. Gene considering significant
difference in serum TC, TG, HDL-C, LDL-C and VLDL-C levels (P<0.001, <0.0001) of patients and control samples.
In CAD patients, G allele frequency is less than A allele frequency. G allele is responsible for decreasing the
LDL: HDL ratio which shows evidence in having its protecting effect on the occurrence of CAD in West Bengal Population.
Key-words- CAD, PCSK9, SNP, Eam1104I, Polymorphism, West Bengal population
Making genome edits in mammalian cellsChris Thorne
Looking at the kind of modifications that can be made in mammalian cells, and how at Horizon moving to a haploid model system has significantly improved efficiency of both editing and validation
Cancer Research: Effects of Insulin-like Factor -2 (IGF-2), Collagen, and Fib...Raul Soto
Cancer Research: Effects of Insulin-like Factor -2 (IGF-2), Collagen, and Fibronectin on the Proliferation and α5-Integrins Expression of the Rhabdomyosarcoma-derived (RD) Cell Line
Targeted T-cell receptor beta immune repertoire sequencing in several FFPE ti...Thermo Fisher Scientific
T-cell receptor beta (TCRβ) immune repertoire analysis by next-generation sequencing is a valuable tool for studies of the tumor microenvironment and potential immune responses to cancer immunotherapy. Here we describe a TCRβ sequencing assay that leverages the low sample input requirements of AmpliSeq library preparation technology to extend the capability of targeted immune repertoire sequencing to include FFPE samples which can often be degraded and in short supply
ABSTRACT- Coronary artery disease (CAD) is suspected as a leading cause of mortality in developed countries. Due
to cholesterol and fat deposit plaque is forming into the inner walls of the arteries of the heart, which leads to narrowing
of blood vessels of heart and reduce the blood flow rate into heart. Proprotein convertase subtilisin-like kexin type 9
(PCSK9) is one of the candidate gene that regulate lipoprotein retention pathway of CAD development. It is a newly
discovered serine protease that plays a key role in LDL-C homeostasis by mediating LDL receptor (LDLR). The LDL
receptor is breakdown through a post transcriptional mechanism and induces the production of very low-density
lipoprotein in the fasting state. The aim of this study was to investigate the frequency of single nucleotide
polymorphism (SNP) of PCSK9 gene of 155 CAD patients and 102 ages matched healthy controls. Serum lipids
including total cholesterol (TC), triglycerides (TG), HDL, LDL, and VLDL were analyzed. PCR-RFLP analysis was
carried out to genotype regions carrying Eam 1104I restriction site in the PCSK9. Gene considering significant
difference in serum TC, TG, HDL-C, LDL-C and VLDL-C levels (P<0.001, <0.0001) of patients and control samples.
In CAD patients, G allele frequency is less than A allele frequency. G allele is responsible for decreasing the
LDL: HDL ratio which shows evidence in having its protecting effect on the occurrence of CAD in West Bengal Population.
Key-words- CAD, PCSK9, SNP, Eam1104I, Polymorphism, West Bengal population
KDM5 epigenetic modifiers as a focus for drug discoveryChristopher Wynder
A summary presentation of my scientific work.
My laboratory focused on an enzyme KDM5b (aka PLU-1, JARID1b) that was widely expressed during development and played a key role in progression of breast cancer through HER-2.
My lab focused on understanding the key biochemical activity of the enzyme through dissecting the proteomic and genomic interactors.
Our results were confirmed through the use of ES cells, adult stem cells and mouse models.
Much of this work remains unpublished, please contact me for more information and/or access to any reagents that I still have as part of this work.
crwynder@gmail.com
Evaluation of the lacZ gene in Escherichia coli mutagenesis using pBluescript...Emilio Solomon
This was a research paper I wrote for my Integrated Laboratory Techniques in Biological Sciences II course.
Evaluation of the lacZ gene in Escherichia coli mutagenesis using pBluescript and pTn5: Km vectors
Developmental cascade of morphogens Define Drosophila Body PlanDouglas Easton
The expression of genes in specific regions of the early Drosophila embryo determine the anterior-posterior and dorso-ventral axes of the organism. Expression of these genes are both spatially and temporally coordinated.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
The ASGCT Annual Meeting was packed with exciting progress in the field advan...
Chromatin looping as a target for altering gene expression
1. Chromatin looping as a target for altering erythroid
gene expression
Ivan Krivega, PhD
Laboratory of Cellular and Developmental Biology, NIDDK, NIH
2. How do different cell and tissue types arise?
Changes in gene expression drive developmental progression
The activity of enhancers underlies cell-specific transcription patterns
Enhancers contact genes over long distances
protein
complex
gene
enhancer
Krivega, Dean. Curr Opin Genet Dev. 2012.
3. Questions:
1. How do enhancers loop to target genes?
2. Can loops be manipulated to change disease-associated
gene expression?
4. Questions:
1. How do enhancers loop to target genes?
• role of looping factor LDB1
2. Can loops be manipulated to change disease-associated
gene expression?
5. The mammalian β-globin loci
Locus control region (LCR) enhancer loops to genes
determining which one is active as development proceeds
Tolhuis et al, Mol. Cell, 2002
Palstra et al, Nat. Genet., 2003
adult embryo
mouse
bmajbmin bh1 ey 10 kb
LCR
eGgAgdb
fetusadult OR genesembryo
human
LCR
Drissen et al, Genes Dev., 2004
Vakoc et al, Cell, 2005
Song et al. Mol. Cell, 2007
Yun et al, NAR, 2014
LDB1 complex
6. LDB1
NLSdimerization domain (DD) LIM interaction domain
(LID)
N C
Orthologue of D.melanogaster Chip, cloned in a screen for enhancer facilitators
Highly conserved, no DNA-binding or enzymatic activity, widely expressed
Morcillo et al, Genes Dev., 1997
Muhopadhyay et al, Development, 2003
Wadman et al, EMBO J, 1997
Required for erythropoiesis
WT Ldb1 null
E8.5 embryo
no blood
LID
LIM1 LIM2LMO2
LDB1
23. LDB1 DD 4/5 region is required for proper activation of
blood disease-associated genes
V205M mutation of GATA-1 abolishes
its interaction with FOG1 and causes
X-linked dyserythropoietic anemia
(Nichols et al., Nature Genetics, 2000)
Human disease-associated
homologs from OMIM
4/5-dependent
genes
4/5-independent
genes
Mouse gene
Human homolog
Disease association
(OMIM base)
0
5
10
15
20
25
30
35
4/5-dependent
4/5-independent
all
p=.001
p=.93
%ofdiseaseassociatedgenes
blood related diseases others
Krivega, Dale, Dean. Genes Dev. 2014
24. Questions:
1. How do enhancers loop to target genes?
• role of looping factor LDB1
2. Can loops be manipulated to change disease-
associated gene expression?
• forced looping
25. 0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
HS3 HS2 HS1 εy βh1 βmaj βmin mCD4
IgG
HA
enrichment
0
0.5
1
1.5
2
2.5
3
103658500 103678500 103698500 103718500
BglII
Control
βZF-DD
Induced Control
βmin βmaj βh1 εy
HS2
interactionfrequency
Forced LCR looping using ZF-DD
G1E+GATA1
0
1
2
3
4
5
6
7
relativeexpression
βmaj
G1E
Deng et al, Cell, 2012
DD
βZF-DD
βZF HA
G1E cells (GATA1 null)
no βmaj expression
26. Forced LCR looping using dCas9-DDΔ4/5
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
HS5 HS4 HS3 HS2 HS1 ey βh1 β-major β-minor 3'HS1 necdin
HA Control
HA βmaj-DDΔ4/5
enrichment
0
2
4
6
8
10
12
14
16
0 10000 20000 30000 40000 50000 60000 70000
BglII
Control
dCas9-DΔ4/5
Induced Control
0
2
4
6
8
10
12
14
16
relativeexpression
βmaj
HS2
βmin βmaj βh1 εy
interactionfrequency
βmaj-DDΔ4/5
UMEL IMEL
Krivega and Dean, Submitted
4/5DD
dCas9-DDΔ4/5
dCas9 HA Uninduced MEL
no βmaj expression
27. Globin gene expression during development
HbF HbA
There are 2 ‘switches’ in globin gene expression
After the γ to b switch, β-thalassemia and sickle cell disease become manifest
Elevated fetal hemoglobin in adults moderates severity of the b-hemoglobinopathies
28. Forced chromatin looping to activated γ-globin genes
expression
e d bS
fetus adultOR genes embryo
human LCR
OR genes
Gg Ag
γZF
LDB1
DD
adult stage
29. Reversal of chromatin looping by γZF-LDB1-DD in
primary human adult erythroid cells
adult
CD34(+)
progenitor cells expansion
5-6 days
differentiation
10-12 days
lentiviral infection GFP sort
γZF DD
Deng*, Rupon*, Krivega et al, Cell, 2014
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
HS2 ε pro γ pro δ pro β pro HS40 α pro CD4
enrichment
IgG
HA
HA
30. interactionfrequency
Reversal of chromatin looping by γZF-LDB1-DD in
primary human adult erythroid cells
εy
0
0.2
0.4
0.6
0.8
1
1.2
5220000 5230000 5240000 5250000 5260000 5270000 5280000 5290000 5300000 5310000 5320000
EcoRI
Control
γZF-DD
Ag Ggδβ
LCR
31. Reactivation of the γ-globin gene in primary human
erythroid cells by γZF-DD
* - p<0.05 by Student’s t-test
0
10
20
30
40
50
60
70
80
90
γZF-DD γZF Control
γ-globin/(γ-globin+β-globin)
% γ-globin of total
* *
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
γZF-DD γZF Control
γ-globin/α-globin
*
*
0
0.5
1
1.5
2
2.5
γZF-DD γZF Control
β-globin/α-globin
γ-globin β-globin
*
*
32. γZF-DD Activates HbF Production
Control
Control
Control Control
Control Control
γZF-DD γZF-DD γZF-DD
γZF-DD γZF-DD γZF-DD
* - p<0.05 by Student’s t-test
34. Model: Manipulation of chromatin loops can overcome
developmental silencing to activate gene expression
γZF DD
Adult erythroid cells
+++
AdultFetal
LCR
LDB1
Adult
+
LCR
Deng*, Rupon*, Krivega et al, Cell, 2014
35. Questions:
1. How do enhancers loop to target genes?
• role of looping factor LDB1
2. Can loops be manipulated to change disease-associated
gene expression?
• forced looping
• pharmacological inhibition of epigenetic factors activity
36. Epigenetic reversal of chromatin looping
g-globin repression
H3K9me2 G9a
MTX
UNC0638
eGgAgdb
LCR
H3K9me2
Phase I-III
UNC0638
UNC0638
UNC0638
0 21
Control
Phase I
7 14
Phase II
Phase III
UNC0638
Days
UNC0638 UNC0638
CD34(+) cells from three
healthy donors were
differentiated ex vivo in 3 phase
serum free culture system
Krivega*, Byrnes* et al, Blood. 2015
expansion differentiation
37. Inhibition of G9a methyltransferase activity in adult human
erythrocytes stimulates fetal hemoglobin production
* - p<0.05 by Student’s t-test
0
5
10
15
20
25
30
35
40
Control Phase I Phase II Phase III Phase I-III
HbF(%)
*
*
*
0
5
10
15
20
25
30
35
0 0.031 0.062 0.12 0.25 0.5 1
HbF(%)
UNC0638 (μM)
*
*
*
*
*
*
0
10
20
30
40
50
60
70
80
90
100
0 0.031 0.062 0.12 0.25 0.5 1
HbF(%)
UNC0638 (μM)
*
43. Model: Epigenetic changes can relieve silencing by allowing
chromatin loops to reactivate gene expression
Adult erythroid cells
G9a
MT
+++
AdultFetal
H3K9me2
LCR
LDB1
Adult
++
LCR
X
Krivega*, Byrnes* et al, Blood. 2015
44. Summary
Enhancer mechanisms: Homodimerization of LDB1 protein through DD domain is
required for looping and transcription activation of b-globin genes.
Expression of blood disease-associated genes depends on interaction between LDB1 and
FOG1 proteins.
Enhancer looping manipulation: In adult erythroid cells, the LCR can be targeted to the
fetal g-globin genes by an ZF-DD based peptide resulting in their re-activation.
Inhibiting G9a methyltransferase activity relieves y-globin silencing in adult erythroid cells
resulting in redistribution of LDB1, LCR looping and g-globin re-activation.
These experiments suggest that chromosome looping can be considered a
therapeutic target for gene activation in b-hemoglobinopathies.
g-globin expression is pan-cellular and is increased to levels
potentially therapeutic in b-thalassemia and sickle cell disease
with balanced decrease in b-globin expression
45. Gene Regulation and Development Section
Laboratory of Cellular and Developmental Biology, NIDDK
Ann Dean
Xiang Guo
Luis Diaz
Ben Leadem
Maria Soledad Ivaldi
Guo-you Liu
Jun Zhang
LCDB Bioinformatics
Ryan Dale
NIDDK Genomics Core
Harold Smith
Collaborators
Jeffery Miller, Colleen Byrnes, Jaira F. de Vasconcellos
NIDDK, NIH
Gerd Blobel, Wulan Deng, Jeremy Rupon
CHOP, Philadelphia, PA
Stefano Rivella, Laura Breda
CHOP, Philadelphia, PA
Acknowledgements