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Ann J. Feeney
Scripps Research Institute
GeneMolecular biologyB cellGeneticsBiology
99Publications
34H-index
4,944Citations
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Publications 99
Newest
#1E. Mauricio Barajas-Mora (UCSD: University of California, San Diego)H-Index: 1
#1Barajas-Mora Em (UCSD: University of California, San Diego)H-Index: 1
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 2 authors...
ABSTRACTEnhancers are defined as regulatory elements that control transcription in a cell-type and developmental stage-specific manner. They achieve this by physically interacting with their cognat...
2 CitationsSource
#1Tessa Arends (University of Colorado Denver)H-Index: 3
#2Carissa Dege (University of Colorado Denver)H-Index: 3
Last. James Hagman (University of Colorado Denver)H-Index: 24
view all 15 authors...
Cell lineage specification is a tightly regulated process that is dependent on appropriate expression of lineage and developmental stage-specific transcriptional programs. Here, we show that Chromodomain Helicase DNA-binding protein 4 (CHD4), a major ATPase/helicase subunit of Nucleosome Remodeling and Deacetylase Complexes (NuRD) in lymphocytes, is essential for specification of the early B cell lineage transcriptional program. In the absence of CHD4 in B cell progenitors in vivo, development o...
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#1Amy L. Kenter (UIC: University of Illinois at Chicago)H-Index: 22
#2Ann J. Feeney (Scripps Research Institute)H-Index: 34
Vast repertoires of unique antigen receptors are created in developing lymphocytes. The antigen receptor loci contain many variable (V), diversity (D), and joining (J) gene segments that are arrayed across very large genomic expanses and are joined to form variable-region exons. This process creates the potential for an organism to respond to large numbers of different pathogens. Here, we consider the underlying molecular mechanisms that favor some V genes for recombination prior to selection of...
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#1James E. Voss (Scripps Research Institute)H-Index: 7
#2Alicia Gonzalez-Martin (CSIC: Spanish National Research Council)H-Index: 9
Last. Dennis R. BurtonH-Index: 139
view all 19 authors...
We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repair strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV broadly neutralizing antibody (bnAb), PG9. Our strategy is designed to function in cells that have undergone VDJ recombination using any combination of variab...
5 CitationsSource
#1E. Mauricio Barajas-Mora (Scripps Research Institute)H-Index: 2
#2Eden Kleiman (Scripps Research Institute)H-Index: 2
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 8 authors...
Summary The genome is organized into topologically associated domains (TADs) that enclose smaller subTADs. Here, we identify and characterize an enhancer that is located in the middle of the V gene region of the immunoglobulin kappa light chain (Igκ) locus that becomes active preceding the stage at which this locus undergoes V(D)J recombination. This enhancer is a hub of long-range chromatin interactions connecting subTADs in the V gene region with the recombination center at the J genes. Deleti...
4 CitationsSource
#1James E. Voss (Scripps Research Institute)H-Index: 7
#2Alicia Gonzalez-Martin (CSIC: Spanish National Research Council)H-Index: 9
Last. Dennis R. BurtonH-Index: 139
view all 19 authors...
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#1Eden Kleiman (Scripps Research Institute)H-Index: 2
#2Jeffrey Xu (Scripps Research Institute)H-Index: 2
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 3 authors...
Igκ locus contraction and Vκ gene usage are controlled by Cer, a cis -acting sequence in the Vκ–Jκ intervening region. This effect is attributed to two CTCF-binding sites within Cer that are oriented toward the Vκ gene region. However, the importance of Cer CTCF orientation in regulating VκJκ rearrangement is unknown. We used CRISPR/Cas9 editing to delete and invert Cer in murine Abl pro–B cell lines. This revealed that Cer orientation is critical because clones with either an inverted or delete...
2 CitationsSource
#1Eden Kleiman (Scripps Research Institute)H-Index: 2
#2Salvatore Loguercio (Scripps Research Institute)H-Index: 11
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 3 authors...
To date there has not been a study directly comparing relative Igk rearrangement frequencies obtained from genomic DNA (gDNA) and cDNA and since each approach has potential biases, this is an important issue to clarify. Here we used deep sequencing to compare the unbiased gDNA and RNA Igk repertoire from the same pre-B cell pool. We find that ~20% of Vk genes have rearrangement frequencies ³2-fold up or down in RNA vs DNA libraries, including many members of the Vk3, Vk4, and Vk6 families. Regre...
1 CitationsSource
#1Salvatore Loguercio (Scripps Research Institute)H-Index: 11
#2E. Mauricio Barajas-Mora (Scripps Research Institute)H-Index: 2
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 5 authors...
CTCF is largely responsible for the 3D architecture of the genome through the creation of long-range chromatin loops. Cohesin is hypothesized to be the main driver of these long-range chromatin interactions by the process of loop extrusion. Here we performed ChIP-seq for CTCF and cohesin in 2 stages each of T and B cell differentiation and examined the binding pattern in all 6 antigen receptor (AgR) loci in these lymphocyte progenitors and in mature T and B cells, ES cells and fibroblasts. The 4...
6 CitationsSource
#1Eden Kleiman (Scripps Research Institute)H-Index: 2
#2Haiqun Jia (Scripps Research Institute)H-Index: 17
Last. Ann J. Feeney (Scripps Research Institute)H-Index: 34
view all 5 authors...
Abstract Ying Yang 1 (YY1) is a ubiquitously expressed transcription factor shown to be essential for pro–B-cell development. However, the role of YY1 in other B-cell populations has never been investigated. Recent bioinformatics analysis data have implicated YY1 in the germinal center (GC) B-cell transcriptional program. In accord with this prediction, we demonstrated that deletion of YY1 by Cγ1-Cre completely prevented differentiation of GC B cells and plasma cells. To determine if YY1 was als...
28 CitationsSource
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